Screening of 1.17 million newborns for inborn errors of metabolism using tandem mass spectrometry in Shanghai, China: A 19-year report.

BACKGROUND: Inborn errors of metabolism (IEMs) frequently result in progressive and irreversible clinical consequences if not be diagnosed or treated timely. The tandem mass spectrometry (MS/MS)-based newborn screening (NBS) facilitates early diagnosis and treatment of IEMs. The aim of this study was to determine the characteristics of IEMs and the successful deployment and application of MS/MS screening over a 19-year time period in Shanghai, China, to inform national NBS policy. METHODS: The amino acids and acylcarnitines in dried blood spots from 1,176,073 newborns were assessed for IEMs by MS/MS. The diagnosis of IEMs was made through a comprehensive consideration of clinical features, biochemical performance and genetic testing results. The levels of MS/MS testing parameters were compared between various IEM subtypes and genotypes. RESULTS: A total of 392 newborns were diagnosed with IEMs from January 2003 to June 2022. There were 196 newborns with amino acid disorders (50.00%, 1: 5910), 115 newborns with organic acid disorders (29.59%, 1: 10,139), and 81 newborns with fatty acid oxidation disorders (20.41%; 1:14,701). Phenylalanine hydroxylase deficiency, methylmalonic acidemia and primary carnitine deficiency were the three most common disorders. Some hotspot variations in eight IEM genes (PAH, SLC22A5, MMACHC, MMUT, MAT1A, MCCC2, ACADM, ACAD8), 35 novel variants and some genotype-biochemical phenotype associations were identified. CONCLUSIONS: A total of 28 types of IEMs were identified, with an overall incidence of 1: 3000 in Shanghai, China. Our study offered clinical guidance for the implementation of MS/MS-based NBS and genetic counseling for IEMs in this city.

A comprehensive clinical evaluation of HER2-TKIs in patients with previously treated HER2-positive metastatic breast cancer.

Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.

Overexpression of ClWRKY48 from Cunninghamia lanceolata improves Arabidopsis phosphate uptake.

MAIN CONCLUSION: Our findings suggested that ClWRKY48 promoted the expression level of Arabidopsis phosphate transporter genes, enhanced phosphate uptake, and delayed the transition from the vegetative stage to the reproductive phase in Arabidopsis. Phosphorus (P) is an essential mineral for plants that influences their growth and development. ClWRKY48, one of the most highly expressed genes in the leaf, was identified by RT-PCR from Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] (C. lanceolata). Furthermore, when treating C. lanceolata with increasing phosphate (Pi) concentration, the expression level of ClWRKY48 rose in leaves, the trends followed the increasing phosphate concentration treatment. ClWRKY48 is a transcription factor in C. lanceolata, according to the results of a yeast one hybridization experiment. Based on subcellular localization studies, ClWRKY48 is a nuclear-localized protein. Under Pi deficiency conditions, the phosphorus concentration of ClWRKY48 overexpressing Arabidopsis increased by 43.2-51.1% compared to the wild-type. Moreover, under Pi limiting conditions, the phosphate transporter genes AtPHT1;1 (Arabidopsis Phosphate transporter 1;1), AtPHT1;4, and AtPHO1 (Arabidopsis PHOSPHATE 1) were expressed 2.1-2.5, 2.2-2.7, and 6.7-7.3-fold greater than the wild-type in ClWRKY48 transgenic Arabidopsis, respectively. Under Pi-sufficient conditions, the phosphorus concentration and phosphate transporter genes of ClWRKY48 overexpression in Arabidopsis are not significantly different from the wild type. These findings indicated that ClWRKY48 increased phosphate absorption in transgenic Arabidopsis. Furthermore, compared to the wild type, the ClWRKY48 transgenic Arabidopsis not only had a delayed flowering time characteristic but also had lower expression of flowering-related genes AtFT (FLOWERING LOCUS T), AtFUL (FRUITFUL), and AtTSF (TWIN SISTER OF FT). Our findings show that ClWRKY48 enhances phosphate absorption and slows the transition from the vegetative to the reproductive stage in ClWRKY48 transgenic Arabidopsis.

Comparison of Depth-Specific Prediction of Soil Properties: MIR vs. Vis-NIR Spectroscopy.

The prediction of soil properties at different depths is an important research topic for promoting the conservation of black soils and the development of precision agriculture. Mid-infrared spectroscopy (MIR, 2500-25000 nm) has shown great potential in predicting soil properties. This study aimed to explore the ability of MIR to predict soil organic matter (OM) and total nitrogen (TN) at five different depths with the calibration from the whole depth (0-100 cm) or the shallow layers (0-40 cm) and compare its performance with visible and near-infrared spectroscopy (vis-NIR, 350-2500 nm). A total of 90 soil samples containing 450 subsamples (0-10 cm, 10-20 cm, 20-40 cm, 40-70 cm, and 70-100 cm depths) and their corresponding MIR and vis-NIR spectra were collected from a field of black soil in Northeast China. Multivariate adaptive regression splines (MARS) were used to build prediction models. The results showed that prediction models based on MIR (OM: RMSEp = 1.07-3.82 g/kg, RPD = 1.10-5.80; TN: RMSEp = 0.11-0.15 g/kg, RPD = 1.70-4.39) outperformed those based on vis-NIR (OM: RMSEp = 1.75-8.95 g/kg, RPD = 0.50-3.61; TN: RMSEp = 0.12-0.27 g/kg; RPD = 1.00-3.11) because of the higher number of characteristic bands. Prediction models based on the whole depth calibration (OM: RMSEp = 1.09-2.97 g/kg, RPD = 2.13-5.80; TN: RMSEp = 0.08-0.19 g/kg, RPD = 1.86-4.39) outperformed those based on the shallow layers (OM: RMSEp = 1.07-8.95 g/kg, RPD = 0.50-3.93; TN: RMSEp = 0.11-0.27 g/kg, RPD = 1.00-2.24) because the soil sample data of the whole depth had a larger and more representative sample size and a wider distribution. However, prediction models based on the whole depth calibration might provide lower accuracy in some shallow layers. Accordingly, it is suggested that the methods pertaining to soil property prediction based on the spectral library should be considered in future studies for an optimal approach to predicting soil properties at specific depths. This study verified the superiority of MIR for soil property prediction at specific depths and confirmed the advantage of modeling with the whole depth calibration, pointing out a possible optimal approach and providing a reference for predicting soil properties at specific depths.

Clinical effect of a novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation for thoracolumbar burst fractures.

BACKGROUND: Short-segment transpedicular screw fixation is a common method for the treatment of thoracolumbar burst fractures (TBFs),but this technique has many problems. Therefore,the purpose of this article is to observe and evaluate the clinical efficacy of a novel transpedicular reducer that we designed for fractured vertebral body reduction and bone grafting in the treatment of TBFs. METHODS: From July 2018 to November 2020, 70 cases of TBFs were included. Thirty-five patients were treated with the novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation (observation group), and 35 patients were treated with short-segment transpedicular screw fixation (control group). Before the operation, after reduction, and 3 days, 3 months,and 12 months after the operation, the two groups were assessed, and compared with respect to the anterior and middle heights of the injured vertebrae, the ratios of the anterior and middle heights of the injured vertebral body to the respective heights of the adjacent uninjured vertebral bodies (AVBHr and MVBHr, respectively), and the Cobb angle of the patients. We compared the pain VAS score and quality of life GQOL-74 score at the last follow-up. Finally,we evaluated the distribution of bone grafts and bone healing 12 months after the operation. RESULTS: The anterior height, middle height, AVBHr, MVBHr, and Cobb angle of the injured vertebral body in the observation after reduction, and 3 days, 3 months and 12 months post-operatively were compared with those of the injured vertebral body before operation. All of these parameters were improved, and the difference was statistically significant (p < 0.05). These parameters in the observation group at the above time points were significantly better than thoes in the control group at the corresponding time points (p < 0.05). The VAS scores at the last follow-up were significantly better than those of the control group (p < 0.05), but the GQOL-74 score differences were not statistically significant (p > 0.05). The observation group showed no obvious defects on CT at 12 months after the operation, and the bone healing was good. CONCLUSION: The novel transpedicular reducer for reduction and bone grafting combined with pedicle screw fixation for TBFs has good clinical efficacy.

Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying gene c.609G>A mutation.

To explore the clinical features and long-term outcomes of patients with cblC type methylmalonic acidemia (MMA) carrying c.609G>A (p.W203X) mutation of gene. The clinical and laboratory findings of 720 patients with MMA carrying the c.609G>A mutation were retrospectively analyzed. There were 172 cases carrying homozygous mutations of c.609G>A (group A), 169 cases carrying compound heterozygous mutations of c.609G>A with c.482G>A (p.R161Q), c.80A>G or c.394C>T (p.R132X) (group B), and 379 cases carrying compound heterozygous mutations of c.609G>A with c.658_660delAAG(p.K220del), c.315A>Tor c.567dupT(p.I190fs13)(group C).The clinical manifestations, the level of blood acylcarnitine, homocysteine and urinary organic acid, and the therapeutic efficacy were compared among groups. Logistic regression was used to analyze the factors influencing the prognosis of patients. There were 306 patients (42.5%) detected from newborn screening, including 156 cases with disease onset; and 414 patients were not detected from the screening, among whom 10 cases were diagnosed by testing after the sibling confirmed, and the remaining 404 were clinical cases. In 560 patients with disease onset, the median onset age is (3 days to 20 years). The onset age of patients in group B was later than that in group A and group C (<0.01). Patients aged mostly manifested as vomiting, diarrhea, feeding difficulties and convulsions, while those year mostly manifested as movement disorders and mental retardation. Patients with renal disease all carried mutations of c.80A>G or c.482G>A, and patients with pulmonary hypertension all carried c.80A>G mutations. A total of 621 cases had long-term follow-up, 156 cases (25.1%) developed well, 433 cases (69.7%) had development delay and 32 cases (5.2%) died. The available data of 559 cases were analyzed by logistic regression, and the results showed that the neonatal screening, disease onset, age of onset and gene mutation site were significantly associated with the prognosis of patients (<0.05 or <0.01). The c.609G>A mutation in gene is associated with early-onset MMA, and most patients, clinical onset occurred within 1 month after birth. The neonatal screening and early treatment can improve the prognosis of patients,whereas clinical onset is unfavorable for prognosis. Patients with c.609G>A homozygous mutation have a worse prognosis than those with the compound heterozygous mutation of c.609G>A with other mutations.

Examining the blood amino acid status in pretherapeutic patients with hyperphenylalaninemia.

BACKGROUND: Hyperphenylalaninemia is the most common genetic metabolic disease. Early treatment prevents brain injury effectively. The present study aimed to detect the exact amino acid status of patients with hyperphenylalaninemia before treatment. METHODS: Data of 116 newborn patients from our Newborn Screening Center and 161 older patients from our clinic before treatment were collected. The content of 17 amino acids in their blood was determined by tandem mass spectrometry and compared with normal controls. Relationship between phenylalanine and other amino acids in patients was analyzed using the smoothing curve fitting and threshold effect analysis. RESULTS: Most amino acids in the blood of patients were within the normal range; however, they were different significantly from those of the normal children. Newborn patients showed higher phenylalanine (346.30 vs 45.90 µmol/L), valine (121.50 vs 110.30 µmol/L), citrulline, ornithine and lower tyrosine (52.97 vs 66.12 µmol/L), threonine (68.68 vs 78.21 µmol/L), glutamine levels than observed in normal newborns. Older patients showed significantly higher phenylalanine (844.00 vs 51.82 µmol/L), valine (117.60 vs 110.90 µmol/L), histidine, serine and lower tyrosine (55.97 vs 67.31 µmol/L), threonine (35.94 vs 51.89 µmol/L), alanine, asparagine, glutamic acid, methionine, arginine, glycine, ornithine, glutamine content than found in matched normal children. Tyrosine, valine, ornithine, and threonine in newborn patients and tyrosine, glycine, glutamine, and threonine in older patients had a nonlinear correlation with phenylalanine levels with obvious threshold effect and clear inflection points. CONCLUSION: Significant difference was observed in the amino acid status between pretherapeutic hyperphenylalaninemia patients and normal children. Some amino acids showed notable threshold effect with phenylalanine level in a nonlinear pattern.

Spatio-temporal variation and source changes of potentially toxic elements in soil on a typical plain of the Yangtze River Delta, China (2002-2012).

The spatio-temporal variation and temporal changes in the sources of Cr, Pb, Cd, Hg, and As in soil on the Hangzhou-Jiaxing-Huzhou (H-J-H) Plain were analysed based on 4,359 soil samples collected in 2002 and 2012. Geostatistical and spatial analysis methods were used to explore the spatio-temporal variation in the pollution levels and 'pollution hotspots' for potentially toxic elements (PTEs), and the positive matrix factor model was used to quantitatively appoint and analyse temporal changes in PTE sources. The results indicated that the PTE content in most parts of the survey area were at a safe level in both 2002 and 2012, but a clearly upward trend was detected for Cr, Pb, and Cd. Moreover the pollution index for Cr, Pb, Cd, and the Nemerow composite pollution index increased in the west but decreased in the east of the H-J-H Plain from 2002 to 2012. The pollution index for Hg and As presented the opposite spatial pattern. It is obvious that there have been changes in the spatial pattern of pollution hotspots for PTEs on the H-J-H Plain from 2002 to 2012. Four sources of PTEs in soil were quantitatively appointed. In 2002, 2012, the dominant sources of Cr, Cd, Hg, and As were soil parent materials, industrial activities, atmospheric deposition and agricultural inputs, respectively. The dominant source of Pb in the soil changed from traffic emissions to soil parent materials, indicating the benefit of banning the use of leaded gasoline in China. This study highlights the importance of monitoring soil environmental quality and highlights the significance of spatio-temporal variation in PTEs in suburban zones or transitional areas undergoing rapid industrialization and urbanization, like the H-J-H Plain.

[Analysis of 12 cases with methylmalonicacidemia cblA type].

OBJECTIVE: To explore the clinical feature, genetic variant and clinical outcome of patients with cblA-type methylmalonic acidemia (MMA). METHODS: Clinical manifestations, therapeutic schedule and prognosis of 12 patients with cblA type MMA were analyzed. MMAA gene variants were analyzed for all patients and their parents. RESULTS: Vomiting, dyspnea and drowsiness were the major clinical features of cblA-type MMA. Eleven patients were vitamin B12-responsive. After treatment, the blood level of propionylcarnitine, ratio of propionylcarnitine/acetylcarnitine, urine level of methylmalonic acid and methylcitric acid have decreased significantly (P< 0.05). Follow-up study showed that 8 patients (66.7%) had normal development, while the rest (33.3%) remained to have various level of mental or movement delay. Fourteen MMAA gene variants were detected, with c.365T>C (p.L122P) being the most common (29.2%). Six novel variants, including c.54delA (p.A19Hfs*43), c.275G>A (p.G92V), c.456delT (p.G153Vfs*8), c.667dupA (p.T223Nfs*4), c.1114C>T (p.Q372X) and c.1137_1138delCA (p.F379Lfs*27) were found. CONCLUSION: The main clinical manifestations of patients with cblA-type of MMA include vomiting, dyspnea and drowsiness. Most patients are vitamin B12-responsive. c.365T>C is a potential hot spot variant of MMAA gene in China.

[Retrospective analysis on clinical data and genetic variations of patients with beta-ketothiolase deficiency].

OBJECTIVE: To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD). METHODS: Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed. RESULTS: Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C5:1) were 0.43 (0.20-0.89) µmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) µmol/L. Both were significantly higher than those of healthy controls (P<0.01). Urinary 2-methyl-3-hydroxybutyric acid was 56.04 (7.69-182.20) and methylcrotonyl glycine was 42.83 (9.20-127.01), both were higher than normal levels. In 5 patients urinary 2-methyl-3-hydroxybutyric acid level was remarkably decreased (P<0.05) after treatment. Analysis of ACAT1 gene mutation was performed in six families. Missense variations were detected in 78.6% of the cases. 42.8% of the 7 BKD patients have carried c.1124A>G (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing. CONCLUSION: Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.

Risk Score for Neurological Complications After Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Procedure-related neurological complications are common after endovascular treatment of unruptured intracranial aneurysms. We aimed to develop a score to quantify individual patient risk. METHODS: We retrospectively analyzed consecutive patients who underwent endovascular treatment for unruptured intracranial aneurysms between January 2012 and September 2015. After excluding those who lost to follow-up and those with fusiform unruptured intracranial aneurysms, included patients were randomly divided into a derivation group (60%) and a validation group (40%). A neurological complication was defined as any transient or permanent increase in the modified Rankin Scale score after aneurysm embolization. A risk score for neurological complications was derived from multivariable logistic regression analyses in the derivation group and validated in the validation group. RESULTS: Overall, 1060 patients were included (636 in the derivation group and 424 in the validation group). The incidence of neurological complications was 5.5% (95% confidence interval, 3.8%-7.4%). A 3-point risk score (S-C-C) was derived to predict neurological complications (size [≥10 mm=1], core areas [yes=1], and cerebral ischemic comorbidity [yes=1]). The incidence of neurological complications varied from 2.2% in 0-point patients to 25.0% in 3-point patients. The score demonstrated significant discrimination (C-statistic, 0.714; 95% confidence interval, 0.624-0.804) and calibration (McFadden R(2), 0.102) in the derivation group. Excellent prediction, discrimination, and calibration properties were reproduced in the validation group. CONCLUSIONS: One in 20 patients will develop neurological complications after endovascular treatment of unruptured intracranial aneurysms. The S-C-C score may be useful for predicting these adverse outcomes based on variables in daily practice.

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes.

BACKGROUND AND OBJECTIVE: Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. METHODS: From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. RESULTS: Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12-47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12-52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3-5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). CONCLUSIONS: Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series.

[Study on the Characterization of VNIR-MIR Spectra and Prediction of Soil Organic Matter in Paddy Soil].

Soil organic matter (SOM) is an essential indicator for the fertility assessment of farmland. and An efficient and stable prediction model is in need to rapidly estimate SOM in larger scale. Spectroscopic technology has been proved as a powerful tool to access SOM in the last decade. The aims of this paper were: to compare different selection method of calibration set for modeling SOM in paddy soil by using visible-near infrared (VNIR), mid-infrared (MIR) and VNIR-MIR spectra and to assess the prediction ability of the results. All spectra were transformed from reflectance to absorbance, and preprocessed by Savitzky-Golay smoothing algorithm. The prediction models of SOM were built by using partial least squares regression (PLSR) coupled with three selection methods of calibration set in VNIR, MIR and VNIR-MIR regions. The selection method of calibration Rank-KS performed better than Rank method and KS method, meanwhile the models in MIR region showed stronger prediction ability than VNIR and VNIR-MIR regions. The best prediction model was obtained with the MIR model combined with Rank-KS, and the root mean square error of prediction (RMSEP) and ratio of performance to deviation (RPD) were 3.25 g·kg-1 and 4.24. According to variable in the projection (VIP) score, important bands for SOM prediction in paddy soil were identified in VNIR and MIR region. Our results show that MIR spectroscopy could make quantitative prediction of SOM in paddy soil and Rank-KS is an effective method for selection of calibration sets, so as to provide some scientific basis for fertility assessment of farmland and rational fertilization.

In situ measurements of organic carbon in soil profiles using vis-NIR spectroscopy on the Qinghai-Tibet plateau.

We wish to estimate the amount of carbon (C) stored in the soil at high altitudes, for which there is little information. Collecting and transporting large numbers of soil samples from such terrain are difficult, and we have therefore evaluated the feasibility of scanning with visible near-infrared (vis-NIR) spectroscopy in situ for the rapid measurement of the soil in the field. We took 28 cores (≈1 m depth and 5 cm diameter) of soil at altitudes from 2900 to 4500 m in the Sygera Mountains on the Qinghai-Tibet Plateau, China. Spectra were acquired from fresh, vertical faces 5 × 5 cm in area from the centers of the cores to give 413 spectra in all. The raw spectra were pretreated by several methods to remove noise, and statistical models were built to predict of the organic C in the samples from the spectra by partial least-squares regression (PLSR) and least-squares support vector machine (LS-SVM). The bootstrap was used to assess the uncertainty of the predictions by the several combinations of pretreatment and models. The predictions by LS-SVM from the field spectra, for which R(2) = 0.81, the root-mean-square error RMSE = 8.40, and the ratio of the interquartile distance RPIQ = 2.66, were comparable to the PLSR predictions from the laboratory spectra (R(2) = 0.85, RMSE = 7.28, RPIQ = 3.09). We conclude that vis-NIR scanning in situ in the field is a sufficiently accurate rapid means of estimating the concentration of organic C in soil profiles in this high region and perhaps elsewhere.

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

BACKGROUND: Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. METHODS: Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. RESULTS: Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. CONCLUSIONS: In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants.

[Endovascular treatment of nongalenic cerebral arteriovenous fistulas].

OBJECTIVE: To explore the efficacies of embolization in the treatment of nongalenic cerebral arteriovenous fistula (NCAVF). METHODS: The clinical data of 16 NCAVF patients (14 from Department of Neurointerventional Medicine, Beijing Tiantan Hospital and 2 from Department of Neurosurgery, Second Municipal Hospital of Yulin) undergoing embolization from April 2008 to October 2014 were analyzed retrospectively. Clinical and imaging follow-ups were conducted. RESULTS: Among them, 6 patients were embolized with coils alone and the remainder coil plus Onyx glue. The digital subtraction angiography (DSA) images obtained immediately after embolization showed that complete (n = 12), near-complete (n = 2) and staged (n = 2) occlusions of NCAVFs were achieved. One patient recurred during an imaging follow-up period of 3-24 months. All symptoms and signs were relieved after embolization during a clinical follow-up period of 3-38 months. CONCLUSION: Embolization with coil or coil-assisted Onyx embolization is both feasible and efficacious for NCAVF. Using coils helps to reduce the velocity of blood flow and assists Onyx in embolizing fistulas in patients with high-flow NCAVF.

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect.

BACKGROUND: In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. METHODS: The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. RESULTS: The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05-2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06-2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29-4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11-2.72) and smoking (OR, 1.86; 95% CI, 1.05-3.29) independently. CONCLUSIONS: Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently.

A Case of Oropharyngeal Syphilis.

We present a case of a 50-year-old male who complained of a sore throat persisting for 2 months. Upon physical examination, multiple mucous patches were observed in the oropharynx region, but no skin lesions were found. Fiberoptic laryngoscopy confirmed these findings. The Treponema pallidum particle agglutination test and toluidine red unheated serum test (TRUST) were positive with a titer of TRUST 1:64. The patient admitted to engaging in extramarital sexual activities with several females but no males. Based on the clinical manifestations and laboratory test results, a diagnosis of secondary syphilis of the oropharynx was established. He was treated with 2.4 million units of benzathine penicillin G by intramuscular injection once a week for 3 weeks. After 1 month, the lesions completely disappeared without any symptoms. The titer of TRUST reduced to 1:2 in 1-year follow-up. This report aims to enhance physicians' understanding and recognition of oropharyngeal syphilis, enabling timely diagnosis and effective management.

Silver-Promoted Three-Component Synthesis of Perfluoroalkenyl Pyrroles through Partial Defluorinative Functionalization of Perfluoroalkyl Halides.

A silver-promoted three-component heterocyclization of alkynes, perfluoroalkyl halides, and 1,3-dinucleophiles was developed for the efficient synthesis of privileged (E)-perfluoroalkenyl pyrroles. The reaction proceeded through a rationally designed sequence of radical perfluoroalkylation and intramolecular defluorinative [3 + 2]-heterocyclization. The utility of perfluoroalkyl halide as a perfluoroalkenyl reagent, by selective and controllable functionalization of two inert C(sp3)-F bonds at vicinal carbon centers on the perfluoroalkyl chain, provides a new reaction mode for the synthesis of value-added organofluorides starting from the easily available and low-cost fluorinated feedstock.

[The technique and application of individualized tympanic membrane flap in the repair of tympanic membrane under endoscopy ear surgery].

Objective:To investigate the technique of personalized flap making under otoscopy and its clinical application. Methods:The clinical data of patients who underwent 301 Military Hospital myringoplasty in the Department of otoendoscopic surgery, Department of Otorhinolaryngology, head and neck surgery, Department of Otorhinolaryngology, from October 2022 to 2023 August were analyzed retrospectively, all enrolled patients were performed independently by the same skilled otoendoscopic surgeon. The patients' general condition, medical history, tympanic membrane perforation scope, perforation size, need for tympanic cavity exploration, thickness of skin flap, tympanic cavity lesion scope, skin flap making method and postoperative rehabilitation were collected. Results:Many factors such as the location of tympanic membrane perforation, the thickness of the skin flap, the degree of curvature or stricture of the ear canal and the extent of the lesion in the tympanic cavity should be considered in the manufacture of the individualized tympanic membrane skin flap, the way of skin flap making does not affect the long-term postoperative rehabilitation, but it can effectively avoid unnecessary ear canal skin flap injury and improve the operation efficiency. Conclusion:Scientific flap fabrication is important for improving surgical efficiency and enhancing surgical confidence.